Peste des petits ruminants (PPR) is a virus disease of sheep and goats in West Africa. When first described, the virus was considered a variant of rinderpest virus. The biological and physicochemical characteristics of the virus indicate that it is closely related to measles, rinderpest and canine distemper viruses. These three viruses form the genus Morbillivirus of the Paramyxoviridae. PPR virus is sufficiently distinct from these 3 viruses to justify considering it as the fourth member of the Morbillivirus genus.
In our effort to develop agents for the treatment of influenza, a phenotypic screening approach utilizing a cell protection assay identified a series of azaindole based inhibitors of the cap-snatching function of the PB2 subunit of the influenza A viral polymerase complex. Using a bDNA viral replication assay (Wagaman, P. C., Leong, M. A., and Simmen, K. A. Development of a novel influenza A antiviral assay. J. Virol. Methods 2002, 105, 105-114) in cells as a direct measure of antiviral activity, we discovered a set of cyclohexyl carboxylic acid analogues, highlighted by VX-787 (2). Compound 2 shows strong potency versus multiple influenza A strains, including pandemic 2009 H1N1 and avian H5N1 flu strains, and shows an efficacy profile in a mouse influenza model even when treatment was administered 48 h after infection. Compound 2 represents a first-in-class, orally bioavailable, novel compound that offers potential for the treatment of both pandemic and seasonal influenza and has a distinct advantage over the current standard of care treatments including potency, efficacy, and extended treatment window.
Isolates of sheep pox and goat pox from Nigeria, Sudan, Kenya, Yemen Arab Republic, Turkey, Pakistan and India were inoculated into British breeds of sheep and goats. Although the isolates displayed a host preference the gross clinical pathology of the disease produced by the different isolates was indistinguishable. The Yemen, Nigeria and India isolates could not be distinguished using homologous and heterologous antisera in neutralisation tests. Animals that had recovered from infection with one isolate were resistant to challenge with any of the other isolates and a single vaccine for use against sheep pox and goat pox is described. The classification of the malignant pox diseases of sheep and goats is discussed.
Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry is combined off-line with rapid chemical quench-flow methods to investigate the pre-steady-state kinetics of a protein-tyrosine phosphatase (PTPase). PTPase kinetics are generally interrogated spectrophotometrically by the employment of an artificial, chromophoric substrate. However, that methodology places a constraint on the experiment, hampering studies of natural, biochemically relevant substrates that do not incorporate a chromophore. The mass spectrometric assay reported herein is based on the formation of a covalent phosphoenzyme intermediate during substrate turnover. This species is generated in the reaction regardless of the substrate studied and has a molecular weight 80 Da greater than that of the native enzyme. By following the appearance of this intermediate in a time-resolved manner, we can successfully measure pre-steady-state kinetics, regardless of the incorporation of a chromophore. The strengths of the mass-spectrometric assay are its uniform response to all substrates, simple and direct detection of covalent enzyme-substrate intermediates, and facile identification of enzyme heterogeneities that may affect enzymatic activity.
Serological evidence was used to confirm an outbreak of Akabane disease in cattle in the Turkish Province of Aydin in 1980. Thereafter, serum collections from the Middle East were screened for the presence of neutralizing antibodies to Akabane virus. The results indicate that the virus was present in a number of provinces on the south Turkish coast in 1979 and 1980 but that it probably did not persist into 1981; the virus had also been present on Cyprus in 1980 and on at least one previous occasion. There was also evidence of limited virus transmission in the Orontes river valley in Syria in 1979 and less precise evidence to show that occasional infection occurred in the lower Jordan river valley. The failure of Akabane virus to persist in southern Turkey for more than two years indicates that this area is open to epidemic rather than endemic infection. The presence of neutralizing antibodies in the eastern Turkish Provinces of Gaziantep and Diyarbakir suggests that this might be the route whereby Akabane virus occasionally invades the Middle East region.
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